Method for preparing optically pure 3-amino butyl alcohol

Abstract

The invention discloses a method for preparing optical pure 3-aminobutanol, which comprises the following steps: acetylacetic ester and chiral phenethylamine react to generate 3-(1'-benzylmethylamine)-2-crotonate enantiomer, namely 3-(1'-benzylmethylamine)-2-crotonate; potassium borohydride triacetate or sodium borohydride triacetate is used to reduce the 3-(1'-benzylmethylamine)-2-crotonate enantiomer into a 3-(1'-benzylmethylamine)-2-butyric ester enantiomer; then chiral pure 3-(1'-benzylmethylamine)-2-butyric ester is obtained through salification and resolution; and the 3-(1'-benzylmethylamine)-2-butyric ester is subject to reducing debenzylation by palladium-carbon to obtain the optical pure 3-aminobutanol. The method has low cost and high product purity, and is suitable for industrialized production.

Description

technical field [0001] The present invention relates to the preparation of chiral drugs. In particular, it relates to a preparation method of optically pure 3-aminobutanol as a chiral drug intermediate. Background technique [0002] Optically active 3-aminobutanol is a key intermediate of many chiral drugs, such as J.O.C., (Journa l oforganic chemistry) 42, 1650, 1977 reports that it is an important intermediate of anticancer drugs; Tetrahedron Lett.29, 231, 1988 , reported that it is an important intermediate in the synthesis of penem antibiotics because it can be derivatized to β-lactam. However, due to the direct resolution method used in the preparation process, many difficulties have been brought about, and 3-aminobutanol has high water solubility and is not easy to extract, so it is difficult to synthesize it. [0003] The synthesis method of this compound mainly contains, one is Russ.J.of Bio.Chem.30,396,2004 report, 3-aminobutanol is obtained by reduction of chiral...

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Problems solved by technology

[0013] This route uses crotonate as a raw material to react with chiral phenethylamine to generate a group of diastereoisomers with two chiral centers. After separation through a silica gel column, a single isomer is obtained and then undergoes ester reduction and debenzylation. Obtain 3-aminobutanol V, this route step is less, and raw material is easy to get, is a kind of method of hopeful suitability for industrialized production, but still has following problem: because the e.e. value of the first step gained product is close to 0, so split The process loss is large and it is difficult to split; the second is that the split process uses the method of column chromatography, which is not suitable for industrial production; the third is that the expensive and very dangerous lithium tetrahydrogen aluminum is used as the reducing agent, and it cannot be scaled up for production.

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